DNA replication is being studied using primarily electron microscope techniques. The systems under study are the Salmonella phage P22 and hybrid phages between P22 and coliphage lambda in which the P22 DNA replication genes (including the origin of replication) and regulation genes are substituted for the analogous genes of lambda. Thus, essentially the same genome is being replicated in the same host (E. coli) by two different DNA replication systems. The aim of the research is to discover the topological forms assumed by replicating molecules of P22, lambda immP22 (the hybrid) and lambda. Particular attention is being devoted to the distinction between symmetric and asymmetric replication of the two complementary DNA strands. The origin of replication of P22 DNA is being located by partial denaturation mapping. The origin of the short fragments of DNA implicated as intermediates in DNA synthesis ("Okazaki fragments") is being studied by physical methods. The aim is to discover whether the production of these fragments is symmetric at a given replication fork. To this end, sensitive methods for hybridization of Okazaki fragments to particular regions of the lambda genome are being developed.